Office of Human Research
Page Title

SOP No.: 505    STUDY CLOSEOUT

Author:    Office of Human Research

Effective Date:  October 1, 2007

Supercedes document dated:              N/A

Last Reviewed on:     N/A                                 

Results of Review:               N/A

This SOP pertains to:  A clinical site conducting FDA-regulated human subject research sponsored by faculty (i.e., Investigators) within Thomas Jefferson University .

Responsibility for executing this SOP:  Investigator and Designated Research Personnel

Approved By:

 

J. Bruce Smith, MD

 

Associate Vice President for Research

 

(signature on file at OHR)

Approved By:

 

Steven E. McKenzie, MD, Ph.D.

 

Vice President for Research

 

(signature on file at OHR)

 

1. INTRODUCTION AND PURPOSE

This procedure describes the activities performed to close out a study at an investigative site.

2. GENERAL INSTRUCTIONS AND RESPONSIBILITIES

  1.  The Investigator is responsible for final review and determination that the Investigator's obligations have been met and all applicable study and regulatory requirements have been fulfilled at the conclusion of a clinical study.

  2. The Sponsor/ Monitor is responsible for completing and documenting all study closeout activities and obligations.

  3. The Investigator is responsible for keeping the Office of Human Research apprised of plans to suspend or terminate any clinical site and inform the IRB if such plans are to be carried out.

  4. The Investigator will make the final determination that the Investigator's obligations have been met and that all study and regulatory requirements have been fulfilled.
  5. The objectives of the closeout visit are to:
    • Review the Investigator's file to ensure all required documents and records are on file
    • Confirm the disposition of the investigational product and other ancillary items
    • Review records retention and study reporting requirements

3. SPECIFIC PROCEDURES

3.1 Site Closeout for Completion of Enrollment

  1. A study site closeout visit is conducted when the requirements of the protocol have been satisfied, the site Investigator has enrolled the number of participants that were specified in the protocol and the Investigator has followed the participants for the duration of time specified in the protocol.
  2. The Sponsor's designee will contact the participating site Investigator to arrange a closeout visit according to the Data Safety Monitoring Plan after the last participant has concluded his/her participation.
  3. The Sponsor will designate a Monitor to conduct that visit.
  4. The Monitor will review previous Monitor's reports to assess the scope of documentation that must be available for review and collection.

3.1.1 Site Responsibilities Prior to Closeout

At the investigative site, all the following activities are or should be completed by the site personnel prior to the study closeout visit:

  1. All participants must complete all study visits.
  2. The site Investigator reviews all case report forms (CRFs) and source documents to verify accuracy and completion before the Monitor's closeout visit.
  3. The Investigator completes all requests for data corrections or verifications on CRFs, and returns them to the Investigator.
  4. All unused investigational products are collected from all participants.
  5. All used and unused investigational products are inventoried.
  6. The used and unused investigational products are returned to the Investigator in the manner specified.
  7. Copies of the investigational product logs, final inventory and return documents are filed in the study file.
  8. All other Investigator-required reports are completed, with copies in the study file and sent to the Investigator.
  9. The Investigator collects information for Institutional Review Board (IRB) study closure, sends a final report to the IRB, sends a copy to the Investigator and retains a file copy.
  10. The Investigator or designee reviews the study file and recovers any missing documents or places an explanation in the file.
  11. The designee stores CRFs, source documents, and study files, and informs the Investigator of the storage location.

3.1.2 Monitor Responsibilities

At the investigative site, all the following activities are completed by the Monitor to close out the study:

  1. Collect all remaining CRFs and update any outstanding data corrections tabulations
  2. Review the Investigator's study files to ensure that all study documentation is current and complete
  3. Review signed informed consent forms for all participants enrolled since the last monitoring visit and compare with the Investigator's participant enrollment records, as well as any screening failures, if required by the protocol
  4. Reconcile and collect original investigational product accountability records
  5. Ensure that copies of accountability records are made and maintained for the site
  6. Arrange to have remaining unused investigational product and other study incidentals and accessories shipped back to the Investigator if the site has not already done so
  7. Verify that all specimens for laboratory studies have been forwarded to the appropriate location
  8. Remind the site Investigator to inform the IRB of the completion of the study and file the appropriate final report, if the Investigator has not already done so
  9. Instruct the site Investigator to submit a final report of the study to the Investigator within 90 days, if the Investigator has not already done so
  10. Discuss the requirements for maintaining clinical study documentation after the completion of the study for the period of time specified in applicable regulations
  11. Confirm that documentation exists of all prior visits by Monitors and other authorized parties (See SOP 402 Attachment C, Site Visit Log)
  12. The Monitor will forward all pertinent data and other information to the Investigator
  13. Complete the Close-out Visit Report to document the closeout visit (See SOP 505, Attachment A)

3.2 Suspension Due to Inadequate Enrollment

  1. A clinical study site may be suspended when participant enrollment has been insufficient and the terms of the clinical protocol and clinical study contract are not met.
  2. Periodic assessments of enrollment by the Investigator form the basis for decisions to suspend a protocol for inadequate enrollment. The Investigator should determine whether site enrollment is on schedule in regards to timelines and enrollment projections.
  3. If enrollment is lagging behind schedule, the Investigator should  ascertain possible remedies to restore desired rate of enrollment (e.g., additional recruitment efforts).
  4. If enrollment is not expected to reach optimum levels, the Investigator must decide if the site should continue enrolling participants at the current rate, and apprise OHR of the decision.
  5. If continuing enrollment is determined to not be in the best interest of the study, the Investigator will advise the sponsor that the site will  suspend enrollment per terms defined in the contract, and will confirm the decision in writing.
  6. The Investigator or his/her designee will establish a schedule for conducting a closeout visit when all follow-up on existing participants has been completed.
  7. The site Investigator will report the suspension of the study to the IRB and other appropriate regulatory authorities.
  8. If a decision is made to terminate the site, the Sponsor/ Monitor will conduct the closeout visit per procedures outlined above.

3.3 Study Termination

  1. A clinical study site may be terminated before the designated time period if participants are placed at unreasonable risk, if the terms of the clinical protocol are violated, or by FDA order.
  2. If FDA orders the Sponsor to terminate a study, the Investigator will immediately contact all participating Co- Investigators to notify them of the termination.
  3. If the Investigator becomes aware of any circumstance that puts study participants at unreasonable risk, he/she will proceed to terminate the study by contacting all participating Co- Investigators of the termination, and by apprising OHR and the IRB of that decision.
  4. During routine monitoring visits, if the Sponsor observes or otherwise discovers protocol violations, the Sponsor/ Monitor should document the findings and meet with the Investigator immediately upon completing the monitoring visit to present the findings.
  5. Protocol violations may result in study participants being put at risk or rendering the study data untrustworthy. Examples of protocol violations include:
    • Enrolling of subjects or failure to document using the investigational product in a manner not specified by the clinical protocol
    • The reporting of inaccurate or fraudulent data revealed during routine monitoring of source documents
    • Failure to apply correct randomization procedures when conducting randomized studies
    • Continual failure to conduct and report on required routine follow-up assessments
    • Failure to employ adequate stock control or investigational product accountability procedures
  6. The Sponsor will ascertain whether the violation(s) is (are) new or represent an ongoing pattern of non-compliance.
  7. The Sponsor will also ascertain the severity of the violation(s), such that either a warning or immediate termination is the appropriate follow-up action.
  8. If the site is otherwise in compliance with the protocol and without a history of prior non-compliance, the Sponsor should contact the site Investigator and discuss the violation(s), requesting that no further violations be permitted to occur (warning).
  9. If a pattern of non-compliance is ascertained at the site, or if the violations are so severe that participants are at risk of serious injury, the Sponsor will contact the site Investigator and advise him/her that the study has been terminated effective immediately and the reason(s) for the termination.
  10. The Investigator will be advised to cease enrolling participants immediately and report the study termination to the IRB and any other appropriate internal and external regulatory authorities. The Investigator should consult with the OHR regarding the particular notification requirements for a specific situation.
  11. The Investigator will create a plan of action for managing participants already enrolled to assure appropriate transition off study (e.g., may need to taper off study agent or need other medical treatment, etc.)
  12. The Sponsor will confirm all verbal discussions with the site Investigator by follow-up letter via Certified Mail Return Receipt.
  13. As with suspension, participant enrollment is discontinued at the site but the closeout visit cannot occur until all enrolled study participants have completed their specified follow-up visits and have completed their participation in the study.
  14. The Investigator will schedule an immediate monitoring visit to retrieve all unused investigational product and current study documentation.
  15. The Investigator will schedule a final closeout visit after all participant follow-up visits have been completed.

4. APPLICABLE REGULATIONS AND GUIDELINES

21 CFR 312.50

General responsibilities of sponsors

21 CFR 312.56

Review of ongoing investigations

21 CFR 312.59

Disposition of unused supply of investigational drug

21 CFR 312.60

General responsibilities of investigators

21 CFR 312.62

Investigator recordkeeping and record retention

21 CFR 312.64

Investigator reports

21 CFR 312.66

Assurance of IRB review

21 CFR 312.68

Inspection of investigator's records and reports

January 1988

Guidelines for the Monitoring of Clinical Investigations

May 1997

International Conference on Harmonisation; Good Clinical Practice: Consolidated Guideline

5. REFERENCES TO OTHER APPLICABLE SOPs

GA-102

Responsibilities of the Research Team

PM-301

Site-Sponsor/CRO Communications

PM-303

Regulatory Files and Subject Records

PM-306

Investigational Drug Accountability, Storage, Dispensing and Return

DM-501

Data Management

QA-601

Audits

6. ATTACHMENTS

A. Closeout Visit Report

7. DEFINITIONS AND GLOSSARY

The following definitions from the International Conference on Harmonisation, Good Clinical Practice: Consolidated Guideline, apply to this SOP.

Audit: A systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted, and the data were recorded, analyzed, and accurately reported according to the protocol, sponsor’s standard operating procedures (SOPs), good clinical practice (GCP), and the applicable regulatory requirement(s).

Clinical Trial/Study Report: A written description of a trial/study of any therapeutic, prophylactic, or diagnostic agent conducted in human subjects, in which the clinical and statistical description, presentations, and analyses are fully integrated into a single report.

Monitoring: The act of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the protocol, standard operating procedures (SOPs), GCP, and the applicable regulatory requirement(s).

Source Documents: Original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments involved in the clinical trial).

 

back to PM-500 index


Click to leave feedback
feedback